Locomotor analysis identifies early compensatory changes during disease progression and subgroup classification in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.

Numerical Application of the Flamelet Model to Supersonic Turbulent Combustion

In this study,the flow field structure inside a scramjet combustor is numerically simulated using the flamelet/progress variable model.Slope injection is considered,with fuel mixing enhanced by means of a streamwise vortex.The flow field structure and combustion characteristics are analyzed under different conditions.Attention is also paid to the identification of the mechanisms that keep combustion stable and support enhanced mixing.The overall performances of the combustion chamber are discussed.

连续变速颤振试验信号处理的递推时频分析方法(英文)

Focused on the non-statlonarity and real-time analysis of signal in flutter test with progression variable speed （FTPVS）, a new method of recursive time-frequency analysis is presented. The time-varying system is tracked on-line by building a time-varying parameter model, and then the relevant parameter spectrum can be obtained. The feasibility and advantages of the method are examined by digital simulation. The results of FTPVS at low-speed wind-tunnel promise the engineering application perspective of the method.